Buprenorphine is a semi-synthetic opiate with partial agonist and antagonist actions. As such, it is a powerful analgesic that is approximately twenty-five to forty times as potent as morphine and is indicated for the treatment of moderate to severe chronic pain or for pre-operative analgesia. Buprenorphine is also used to treat opiate addiction. Accordingly, the demand for buprenorphine is increasing. Processes for synthesizing buprenorphine have been known since the late 1960s; it is traditionally made from either thebaine or oripavine in seven or more steps. Not only is the overall yield low (typically less than 10%), but the final product has levels of impurities that exceed the currently prescribed guidelines established by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and the United States Pharmacopeial Convention (USP).
More efficient processes are being developed to increase the yield of buprenorphine while minimizing the formation of side products, and to ensure that the final product has a level of purity that meets current ICH and USP standards. However, even the more efficient processes may still be relatively ineffective at avoiding or eliminating side products that are chemically similar to the desired buprenorphine product. For example, side products of buprenorphine synthesis such as Impurity A (2-[17-(but-3-enyl)-4,5α-epoxy-3-hydroxy-6-methoxy-
6α) having Formula (I) above is similar chemically to buprenorphine, shown above as Formula (II)
Impurity A may be formed during the synthesis of buprenorphine, and is difficult to separate from the desired buprenorphine product using existing techniques such as liquid phase separation and crystallization due to the similar chemical structure and properties of Impurity A to buprenorphine. A need exists for a method of eliminating chemically similar side products from crude buprenorphine, resulting in a final product with a level of purity that meets current ICH and USP standards.